The Menstrual Cycle: Phases and Hormones

Overview: The Hypothalamic-Pituitary-Ovarian (HPO) Axis

The menstrual cycle is an exquisite example of hormonal feedback regulation — involving the hypothalamus, anterior pituitary, and ovaries working in a precisely timed cascade. The four key hormones are:

• GnRH (gonadotropin-releasing hormone) — from the hypothalamus
• FSH (follicle-stimulating hormone) — from the anterior pituitary
• LH (luteinizing hormone) — from the anterior pituitary
• Estrogen and Progesterone — from the ovaries (primarily)

The average cycle is 28 days (range: 21–35 is considered normal). Cycle length and characteristics vary considerably among individuals and across a lifetime. The "day 1" convention refers to the first day of menstrual bleeding.

Phase 1: Menstruation (Days 1–5)

Menstruation is simultaneously the end of the previous cycle and the beginning of the new one. It is triggered when the previous cycle's corpus luteum degenerates — causing a precipitous drop in progesterone and estrogen levels.

What happens in the uterus: Without progesterone support, the spiral arteries in the endometrium constrict, causing ischemia (lack of blood flow). The endometrial lining — built up over the previous cycle in preparation for possible implantation — begins to detach and shed as menstrual flow, which consists of blood, endometrial tissue, uterine gland secretions, and vaginal epithelial cells. Average blood loss is 30–80 mL over 3–7 days, though this varies widely.

What happens hormonally: Low estrogen and progesterone remove negative feedback on the hypothalamus. The hypothalamus increases GnRH pulse frequency → anterior pituitary releases FSH (and some LH) → ovarian follicles begin developing.

Phase 2: Follicular Phase (Days 1–13)

The follicular phase begins simultaneously with menstruation (both start on day 1) and ends at ovulation. It is characterized by follicle development in the ovary and endometrial proliferation in the uterus — driven by rising estrogen.

Ovarian events: Rising FSH stimulates a cohort of 10–20 primary follicles to begin developing. Each follicle consists of an oocyte (immature egg) surrounded by granulosa cells. As follicles grow, they produce increasing amounts of estradiol (the primary estrogen). Normally, one follicle — the dominant follicle — outpaces the others due to its higher sensitivity to FSH (more FSH receptors), while the others undergo atresia (programmed degeneration). The dominant follicle grows to approximately 20–25 mm in diameter by the end of this phase and is visible on ultrasound.

Uterine events (Proliferative Phase): Rising estrogen stimulates the endometrium to proliferate — the endometrial lining thickens from ~1 mm to ~8–10 mm, with increasing vascularity and glandular growth. This prepares the uterine environment for potential implantation.

Hormonal feedback: Initially, rising estrogen exerts negative feedback on the hypothalamus and pituitary, keeping FSH levels from rising too high (which prevents too many follicles from maturing). As estrogen reaches a critical level (~200 pg/mL sustained for ~36 hours), it switches to positive feedback, triggering the LH surge.

Phase 3: Ovulation (Day 14 in a 28-day cycle)

Ovulation is triggered by the LH surge — a massive, rapid spike in LH from the anterior pituitary caused by the estrogen-induced positive feedback. The LH surge:

1. Causes the dominant follicle to complete the first meiotic division (the primary oocyte becomes a secondary oocyte).
2. Triggers the release of proteolytic enzymes and prostaglandins that digest the follicle wall.
3. Causes follicle rupture — the secondary oocyte, surrounded by the corona radiata and zona pellucida, is released into the peritoneal cavity and swept into the fallopian tube by fimbriae.

Fertility window: The released oocyte is viable for only 12–24 hours. However, sperm can survive in the female reproductive tract for up to 5 days. Therefore, the fertile window extends from approximately 5 days before ovulation to 24 hours after — days 9–15 in a 28-day cycle.

Ovulation detection: Basal body temperature rises 0.2–0.5°C after ovulation (due to progesterone's thermogenic effect). LH surge can be detected using over-the-counter ovulation predictor kits, typically 24–36 hours before ovulation. Transvaginal ultrasound can directly visualize follicle growth and rupture.

Phase 4: Luteal Phase (Days 15–28)

After ovulation, the ruptured follicle undergoes a dramatic transformation under the influence of LH: it becomes the corpus luteum (yellow body) — a temporary endocrine gland.

The corpus luteum's role: It produces large amounts of progesterone and some estrogen. Progesterone is the dominant hormone of the luteal phase, and it has several critical effects:

• Converts the proliferative endometrium into the secretory endometrium — glands become coiled and begin secreting glycogen-rich fluid (the "uterine milk") that would nourish an early embryo before implantation.
• Increases mucus viscosity in the cervix, preventing sperm entry and pathogen invasion.
• Slightly raises basal body temperature (which is how basal body temperature charting detects ovulation has occurred).
• Exerts negative feedback on FSH and LH, preventing new follicles from developing during the luteal phase.

If fertilization occurs: The embryo (specifically, the trophoblast cells) begins producing hCG (human chorionic gonadotropin) approximately 6–12 days after fertilization. hCG acts like LH — it "rescues" the corpus luteum, preventing its degeneration. The corpus luteum continues to produce progesterone until the placenta takes over (around weeks 9–10 of pregnancy). Urine and blood pregnancy tests detect hCG.

If fertilization does not occur: Without hCG, the corpus luteum undergoes luteolysis — programmed degeneration — approximately 12 days after ovulation. Progesterone and estrogen levels plummet. This hormonal withdrawal triggers menstruation and restarts the cycle.

Common Menstrual Cycle Disorders

PCOS (Polycystic Ovary Syndrome): The most common endocrine disorder in reproductive-age women (affecting 8–13%). Characterized by hyperandrogenism (elevated testosterone — causing acne, hirsutism), irregular or absent ovulation, and insulin resistance. Multiple small follicles develop but none achieves dominance. Diagnosis requires 2 of 3 criteria (Rotterdam criteria): irregular ovulation, biochemical or clinical hyperandrogenism, polycystic ovaries on ultrasound. Leading cause of anovulatory infertility. Management includes lifestyle modification, metformin (for insulin resistance), clomiphene or letrozole (for ovulation induction).

Endometriosis: Endometrial-like tissue implants and grows outside the uterus — most commonly on the ovaries, fallopian tubes, and pelvic peritoneum. Responds to hormonal fluctuations just like the normal endometrium — it proliferates, then bleeds monthly — but the blood has nowhere to go, causing inflammation, adhesions, and severe pain. Affects approximately 10% of women of reproductive age. Average diagnostic delay is 7–10 years. Leading cause of chronic pelvic pain and one of the most common causes of infertility.

Premenstrual Syndrome (PMS) and PMDD: PMS involves physical and psychological symptoms (bloating, breast tenderness, mood changes, irritability, fatigue) in the luteal phase, resolving with menstruation. PMDD (premenstrual dysphoric disorder) is the severe form — debilitating mood disturbance that significantly impairs daily functioning. PMDD responds to SSRIs taken either continuously or only during the luteal phase.

Dysmenorrhea: Painful menstrual cramps. Primary dysmenorrhea (no underlying pathology) is caused by prostaglandin-mediated uterine contractions — treated with NSAIDs (which inhibit prostaglandin synthesis) or hormonal contraceptives. Secondary dysmenorrhea has an underlying cause (endometriosis, fibroids, adenomyosis) and typically requires targeted treatment.